title: Hypermagnesemia does not prevent intracranial hypertension and aggravates cerebral hyperperfusion in a rat model of acute hyperammonemia.
abstract: Intravenous infusion of magnesium sulfate prevents seizures in patients with eclampsia and brain edema after traumatic brain injury. Neuroprotection is achieved by controlling cerebral blood flow (CBF), intracranial pressure, neuronal glutamate release, and aquaporin-4 (Aqp4) expression. These factors are also thought to be involved in the development of brain edema in acute liver failure. We wanted to study whether hypermagnesemia prevented development of intracranial hypertension and hyperperfusion in a rat model of portacaval anastomosis (PCA) and acute hyperammonemia. We also studied whether hypermagnesemia had an influence on brain content of glutamate, glutamine, and aquaporin-4 expression. The study consisted of three experiments: The first was a dose-finding study of four different dosing regimens of magnesium sulfate (MgSO4) in healthy rats. The second involved four groups of PCA rats receiving ammonia infusion/vehicle and MgSO4) /saline. The effect of MgSO(4) on mean arterial pressure (MAP), intracranial pressure (ICP), CBF, cerebral glutamate and glutamine, and aquaporin-4 expression was studied. Finally, the effect of MgSO4 on MAP, ICP, and CBF was studied, using two supplementary dosing regimens. In the second experiment, we found that hypermagnesemia and hyperammonemia were associated with a significantly higher CBF (P < 0.05, two-way analysis of variance [ANOVA]). Hypermagnesemia did not lead to a reduction in ICP and did not affect the brain content of glutamate, glutamine, or Aqp-4 expression. In the third experiment, we achieved higher P-Mg but this did not lead to a significant reduction in ICP or CBF.
  
  
  CONCLUSIONS
  Our results demonstrate that hypermagnesemia does not prevent intracranial hypertension and aggravates cerebral hyperperfusion in rats with PCA and hyperammonemia.
authors.affiliation: Department of Hepatology, Rigshospitalet, Copenhagen, Denmark. peter.nissen.bjerring@rh.regionh.dk
authors.forename: Peter Nissen
authors.initials: PN
authors.lastname: Bjerring
authors.forename: Martin
authors.initials: M
authors.lastname: Eefsen
authors.forename: Fin Stolze
authors.initials: FS
authors.lastname: Larsen
authors.forename: William
authors.initials: W
authors.lastname: Bernal
authors.forename: Julia
authors.initials: J
authors.lastname: Wendon
mesh_terms: D000641:Ammonia / Q000009:adverse effects / Q000097:blood / Q000494:pharmacology; D000818:Animals; D051401:Aquaporin 4 / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D001921:Brain / Q000378:metabolism; D002560:Cerebrovascular Circulation / Q000187:drug effects / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D018698:Glutamic Acid / Q000378:metabolism; D005973:Glutamine / Q000378:metabolism; D022124:Hyperammonemia / Q000097:blood / Q000139:chemically induced / Q000503:physiopathology*; D019586:Intracranial Hypertension / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D007427:Intracranial Pressure / Q000187:drug effects; D008278:Magnesium Sulfate / Q000097:blood* / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D023421:Models, Animal; D051381:Rats; D017208:Rats, Wistar; D012039:Regional Blood Flow / Q000187:drug effects
chemical_list: C496032:Aqp4 protein, rat; D051401:Aquaporin 4; D005973:Glutamine; D018698:Glutamic Acid; D008278:Magnesium Sulfate; D000641:Ammonia